Organization End Tuberculosis Research Articles

The magnitude of unfavorable tuberculosis treatment outcomes and their relation with baseline undernutrition and sustained undernutrition among children receiving tuberculosis treatment in central Ethiopia

BackgroundOne of the global key indicators for monitoring the implementation of the World Health Organization's End Tuberculosis (TB) Strategy is the treatment outcome rate. ObjectiveThis study aims to assess the magnitude of unfavorable treatment outcomes and estimate their relationship with baseline undernutrition and sustained undernutrition among children receiving TB treatment in central Ethiopia. MethodsThis retrospective cohort study included children treated for drug-susceptible TB between June 2014 and February 2022. The study comprised children aged 16 and younger who were treated in 32 randomly selected healthcare facilities. A log-binomial model was used to compute adjusted risk ratios (aRR) with 95% confidence intervals (CIs). ResultsOf 640 children, 42 (6.6%; 95% CI = 4.8–8.8%) had an unfavorable TB treatment outcomes, with 31 (73.8%; 95% CI = 58.0–86.1%) occurring during the continuation phase of TB treatment. We confirmed that baseline undernutrition (aRR = 2.68; 95% CI = 1.53–4.71), age less than 10 years (aRR = 2.69; 95% CI = 1.56–4.61), HIV infection (aRR = 2.62; 95% CI = 1.50–4.59), and relapsed TB (aRR = 3.19; 95% CI = 1.79–4.71) were independent predictors of unfavorable TB treatment outcomes. When we looked separately at children who had been on TB treatment for two months or more, we found that sustained undernutrition (aRR = 3.76; 95% CI = 1.90–7.43), age below ten years (aRR = 2.60; 95% CI = 1.31–5.15), and HIV infection (aRR = 2.26; 95% CI = 1.11–4.59) remained predictors of unfavorable outcomes, just as they had in the first two months. However, the effect of relapsed TB became insignificant (aRR = 2.81; 95% CI = 0.96–8.22) after the first two months TB treatment. ConclusionsThe magnitude of unfavorable TB treatment outcomes among children in central Ethiopia met the World Health Organization's 2025 milestone. Nearly three-quarters of unfavorable TB treatment outcomes occurred during the continuation phase of TB treatment. Baseline undernutrition, sustained undernutrition, younger age, HIV infection, and relapsed TB were found to be independent predictors of unfavorable TB treatment outcomes among children receiving TB treatment in central Ethiopia.

Protocol for the Addressing the Social Determinants and Consequences of Tuberculosis in Nepal (ASCOT) pilot trial.

BACKGROUND:The World Health Organization's End TB (tuberculosis) Strategy advocates social and economic support for TB-affected households but evidence from low-income settings is scarce. We will evaluate the feasibility and acceptability of a locally-appropriate socioeconomic support intervention for TB-affected households in Nepal. METHODS:We will conduct a pilot randomised-controlled trial with mixed-methods process evaluation in four TB-endemic, impoverished districts of Nepal: Pyuthan, Chitwan, Mahottari, and Morang.We will recruit 128 people with TB notified to the Nepal National TB Program (NTP) and 40 multisectoral stakeholders including NTP staff, civil-society members, policy-makers, and ASCOT (Addressing the Social Determinants and Consequences of Tuberculosis) team members. People with TB will be randomised 1:1:1:1 to four study arms (n=32 each): control; social support; economic support; and combined social and economic (socioeconomic) support. Social support will be TB education and peer-led mutual-support TB Clubs providing TB education and stigma-reduction counselling. Economic support will be monthly unconditional cash transfers during TB treatment with expectations (not conditions) of meeting NTP goals. At 0, 2, and 6 months following TB treatment initiation, participants will be asked to complete a survey detailing the social determinants and consequences of TB and their feedback on ASCOT. Complementary process evaluation will use focus group discussions (FGD), key informant interviews (KII), and a workshop with multi-sectoral stakeholders to consider the challenges to ASCOT's implementation and scale-up.A sample of ~100 people with TB is recommended to estimate TB-related costs.Information power is estimated to be reached with approximately 25 FGD and 15 KII participants. CONCLUSIONS:The ASCOT pilot trial will both generate robust evidence on a locally-appropriate, socioeconomic support intervention for TB-affected households in Nepal and inform a large-scale future ASCOT trial, which will evaluate the intervention's impact on catastrophic costs mitigation and TB outcomes. The trial is registered with the ISRCTN ( ISRCTN17025974).

Recent advances in oxazolidinones as antituberculosis agents.

Tuberculosis (TB) is an infectious and fatal disease caused by Mycobacterium tuberculosis (Mtb) and remains a serious public health threat; therefore, the development of new antitubercular agents is a priority for the World Health Organization's End TB strategy and the United Nations' Sustainable Development Goals to eradicate TB. Oxazolidinones are a class of synthetic antibacterial agents with a distinct mode of action developed for the treatment of Gram-positive bacterial infections. Many oxazolidinones exhibit good activity against Mtb, and some are currently in clinical trials for multidrug-resistant TBand extensively drug-resistant TBtherapy. In this review, the mechanism of action, activityand toxicity of oxazolidinonesand recent progress in the research and development of oxazolidinones as anti-TB agentsare summarized.

Tuberculosis Notification

Context: The framework for tuberculosis (TB) notification is one of the components of the World Health Organization's End TB strategy. Notification is essential for estimating the true burden of TB and its control in community which is currently lacking in the private health sector. Aims: The objectives are to identify awareness, willingness, barriers, and preferred methods of TB notification among private practitioners (PPs) in Trichy, South India. Methods: A descriptive cross-sectional study was conducted among 152 doctors working in the private sector and having at least 1 year of clinical experience using nonprobability sampling. A semi-structured, pretested questionnaire was used to obtain details about the general profile, awareness, and willingness regarding TB notification, as well as factors that facilitate and hinder it. Results: Among PPs, 90.7% referred TB cases/suspects to other health facilities and 71.7% were aware that TB notification is mandatory. Only 52.6% and 38.2% were ready to provide the patients' Aadhaar number and bank account details respectively during notification. The most common barriers for notification were: not being aware about the notification procedure (50.7%), lack of time (32.2%), process being tedious (29.6%) and difficulties in getting information from patients (25.7%). Mobile SMS/App/call (74.3%) were preferred by PPs over notification through online (32.2%) and government health staff (26.3%). Conclusions: Although three-fourth of the practitioners were aware and willing to notify TB, more than half of them were not aware about the notification procedure. Improving the awareness on the techniques for notification could motivate PPs to notify TB.

Epidemiology of Tuberculosis and Progress Toward Meeting Global Targets - Worldwide, 2019.

Although tuberculosis (TB) is curable and preventable, in 2019, TB remained the leading cause of death from a single infectious agent worldwide and the leading cause of death among persons living with HIV infection (1). The World Health Organization's (WHO's) End TB Strategy set ambitious targets for 2020, including a 20% reduction in TB incidence and a 35% reduction in the number of TB deaths compared with 2015, as well as zero TB-affected households facing catastrophic costs (defined as costs exceeding 20% of annual household income) (2). In addition, during the 2018 United Nations High-Level Meeting on TB (UNHLM-TB), all member states committed to setting 2018-2022 targets that included provision of TB treatment to 40 million persons and TB preventive treatment (TPT) to 30 million persons, including 6 million persons living with HIV infection and 24 million household contacts of patients with confirmed TB (4 million aged <5 years and 20 million aged ≥5 years) (3,4). Annual data reported to WHO by 215 countries and territories, supplemented by surveys assessing TB prevalence and patient costs in some countries, were used to estimate TB incidence, the number of persons accessing TB curative and preventive treatment, and the percentage of TB-affected households facing catastrophic costs (1). Globally, TB illness developed in an estimated 10 million persons in 2019, representing a decline in incidence of 2.3% from 2018 and 9% since 2015. An estimated 1.4 million TB-related deaths occurred, a decline of 7% from 2018 and 14% since 2015. Although progress has been made, the world is not on track to achieve the 2020 End TB Strategy incidence and mortality targets (1). Efforts to expand access to TB curative and preventive treatment need to be substantially amplified for UNHLM-TB 2022 targets to be met.

Impact of Effective Global Tuberculosis Control on Health and Economic Outcomes in the United States.

Rationale: Most U.S. residents who develop tuberculosis (TB) were born abroad, and U.S. TB incidence is increasingly driven by infection risks in other countries.Objectives: To estimate the potential impact of effective global TB control on health and economic outcomes in the United States.Methods: We estimated outcomes using linked mathematical models of TB epidemiology in the United States and migrants’ birth countries. A base-case scenario extrapolated country-specific TB incidence trends. We compared this with scenarios in which countries achieve 90% TB incidence reductions between 2015 and 2035, as targeted by the World Health Organization’s End TB Strategy (“effective global TB control”). We also considered pessimistic scenarios of flat TB incidence trends in individual countries.Measurements and Main Results: We estimated TB cases, deaths, and costs and the total economic burden of TB in the United States. Compared with the base-case scenario, effective global TB control would avert 40,000 (95% uncertainty interval, 29,000–55,000) TB cases in the United States in 2020–2035. TB incidence rates in 2035 would be 43% (95% uncertainty interval, 34–54%) lower than in the base-case scenario, and 49% (95% uncertainty interval, 44–55%) lower than in 2020. Summed over 2020–2035, this represents 0.8 billion dollars (95% uncertainty interval, 0.6–1.0 billion dollars) in averted healthcare costs and $2.5 billion dollars (95% uncertainty interval, 1.7–3.6 billion dollars) in productivity gains. The total U.S. economic burden of TB (including the value of averted TB deaths) would be 21% (95% uncertainty interval, 16–28%) lower (18 billion dollars [95% uncertainty level, 8–32 billion dollars]).Conclusions: In addition to producing major health benefits for high-burden countries, strengthened efforts to achieve effective global TB control could produce substantial health and economic benefits for the United States.

Should we consider a 'fourth 90' for tuberculosis?

The international community has committed to end the tuberculosis (TB) epidemic by 2030. To facilitate the meeting of the global incidence and mortality indicators set by the World Health Organization's End TB Strategy, the Stop TB Partnership launched the three 90-(90)-90 diagnostic and treatment targets in 2014. In this paper, we argue that a 'fourth 90'-Ensuring that 90% of all people successfully completing treatment for TB can have a good health-related quality of life'-should be considered. Many individuals who successfully complete anti-TB treatment are burdened with lifelong comorbidities-human immunodeficiency virus (HIV) and diabetes mellitus, obstructive and restrictive lung disease, involving lung destruction, cavitation, fibrosis and bronchiectasis, that either pre-existed or developed as a result of TB (e.g., chronic pulmonary aspergillosis), permanent disabilities such as hearing loss resulting from second-line anti-TB drugs, and mental health disorders. These need to be identified during TB treatment and appropriate care and support provided after anti-TB treatment is successfully completed. A 'fourth 90' has also been proposed for the UNAIDS 90-90-90 targets similar in scope to what is being suggested here for TB. Adoption by both HIV and TB control programmes would highlight the current focus on integrated person- and family-centred services.

Figures of the dead: A decade of tuberculosis mortality registrations in South Africa.

South Africa (SA) is committed to reducing tuberculosis (TB) mortality rates in line with the World Health Organization's End TB Strategy and the Sustainable Development Goal (SDG) targets. From mortality reports released by Statistics South Africa, this study analysed reported TB mortality in SA from 2006 to 2016 to inform our understanding of TB mortality and the development of strategies needed to attain the SDG targets. TB mortality includes all deaths reported to the Department of Home Affairs with TB reported as the underlying cause of death based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) definition. Although TB remains the leading cause of death, TB mortality rates in SA have fallen substantially in the past decade. From 2006 to 2016, the number of deaths due to TB plummeted from 76 881 to 29 399 and the proportion of all-cause mortality due to TB more than halved from 13% to &lt;6%. Furthermore, the profile of people dying from TB has changed, with a decrease in the proportion of children aged &lt;15 years, adults of reproductive age (15 - 49) and women, and an increase in the proportion aged ≥50. This change has largely mirrored the overall pattern of deaths in SA, with large decreases in deaths in adults aged 15 - 49, especially women, thought to be because of the scale-up of the antiretroviral treatment programme for HIV. The End TB Strategy target of a 95% reduction in TB mortality by 2035 is achievable in SA. However, sustained effort in high-risk groups together with improved vital registration data are needed to ensure attainment of the target.

Global Epidemiology of Tuberculosis and Progress Toward Achieving Global Targets - 2017.

Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1) and the leading cause of death among persons living with human immunodeficiency virus (HIV) infection, accounting for approximately 40% of deaths in this population (2). The United Nations' (UN) Sustainable Development Goals (3) and the World Health Organization's (WHO's) End TB Strategy (4) have defined ambitious targets for 2020-2035, including a 35% reduction in the absolute number of TB deaths and a 20% reduction in TB incidence by 2020, compared with 2015 (4). Since 2000, WHO has produced annual TB estimates for all countries (1). Global and regional disease estimates were evaluated for 2017 to determine progress toward meeting targets. In 2017, an estimated 10 million incident cases of TB and 1.57 million TB deaths occurred, representing 1.8% and 3.9% declines, respectively, from 2016. Numbers of TB cases and disease incidence were highest in the WHO South-East Asia and Africa regions, and 9% of cases occurred among persons with HIV infection. Rifampicin-resistant (RR) or multidrug-resistant (MDR) (resistance to at least both isoniazid and rifampicin) TB occurred among 3.6% and 18% of new and previously treated TB cases, respectively (5.6% among all cases). Overall progress in global TB elimination was modest in 2017, consistent with that in recent years (1); intensified efforts to improve TB diagnosis, treatment, and prevention are required to meet global targets for 2020-2035.

Global tuberculosis targets and milestones set for 2016-2035: definition and rationale.

>BACKGROUND:Global tuberculosis (TB) targets were set as part of the World Health Organization's End TB Strategy (2016–2035) and the Sustainable Development Goals (2016–2030).>OBJECTIVE:To define and explain the rationale for these targets.>DESIGN:Scenarios for plausible reductions in TB deaths and cases were developed using empirical evidence from best-performing countries and modelling of the scale-up of under-used interventions and hypothetical TB vaccines. Results were discussed at consultations in 2012 and 2013. A final proposal was presented to the World Health Assembly in 2014 and unanimously endorsed by all Member States.>RESULTS:The 2030 targets are a 90% reduction in TB deaths and 80% reduction in TB incidence compared with 2015 levels. The 2035 targets are for reductions of 95% and 90%, respectively. A third target—that no TB-affected households experience catastrophic costs due to the disease by 2020—was also agreed.>CONCLUSION:The global TB targets and milestones set for the period 2016–2035 are ambitious. Achieving them requires concerted action on several fronts, but two things are fundamental: 1) progress towards universal health coverage to ensure that everyone with TB can access high-quality treatment; and 2) substantial investment in research and development for new tools to prevent TB disease among the approximately 1.7 billion people infected.

Addressing the tuberculosis-depression syndemic to end the tuberculosis epidemic.

Tuberculosis (TB) and depression act synergistically via social, behavioral, and biological mechanisms to magnify the burden of disease. Clinical depression is a common, under-recognized, yet treatable condition that, if comorbid with TB, is associated with increased morbidity, mortality, community TB transmission, and drug resistance. Depression may increase risk of TB reactivation, contribute to disease progression, and/or inhibit the physiological response to anti-tuberculosis treatment because of poverty, undernutrition, immunosuppression, and/or negative coping behaviors, including substance abuse. Tuberculous infection and/or disease reactivation may precipitate depression as a result of the inflammatory response and/or dysregulation of the hypothalamic-pituitary-adrenal axis. Clinical depression may also be triggered by TB-related stigma, exacerbating other underlying social vulnerabilities, and/or may be attributed to the side effects of anti-tuberculosis treatment. Depression may negatively impact health behaviors such as diet, health care seeking, medication adherence, and/or treatment completion, posing a significant challenge for global TB elimination. As several of the core symptoms of TB and depression overlap, depression often goes unrecognized in individuals with active TB, or is dismissed as a normative reaction to situational stress. We used evidence to reframe TB and depression comorbidity as the 'TB-depression syndemic', and identified critical research gaps to further elucidate the underlying mechanisms. The World Health Organization's Global End TB Strategy calls for integrated patient-centered care and prevention linked to social protection and innovative research. It will require multidisciplinary approaches that consider conditions such as TB and depression together, rather than as separate problems and diseases, to end the global TB epidemic.

An overview of tuberculosis and migration.

With nearly one billion migrants worldwide, migration is both a dynamic and a divisive phenomenon facing the world today. Migrants are a heterogeneous group, and the conditions surrounding migration pathways often pose risks to the physical, mental and social well-being of migrants, with certain subgroups being more vulnerable than others. Several determinants of health and tuberculosis (TB) interplay to increase the vulnerability of migrants to tuberculous infection, TB disease and poor treatment outcomes, making them a key population for TB. This article is the first in the State-of-the-Art series of the International Journal of Tuberculosis and Lung Disease on TB and migration. It provides an overview of migration trends, migration pathways and social determinants, and impact on TB. This article outlines a framework for the prevention and reduction of the TB burden among migrants, adapted from the World Health Organization's End TB Strategy, and in accordance with the Stop TB Partnership's Global Plan and the Sustainable Development Goals (SDGs) agenda. The framework highlights the need for migrant-inclusive national TB plans, and calls for action across all three pillars of the End TB Strategy for migrant-sensitive care and prevention, bold intersectoral policies and systems supportive of migrants, and operational research. More research is needed on the TB burden and challenges faced by migrants and on the feasibility and effectiveness of approaches proposed here and the scaling up of models already underway. Political commitment at the highest national and international levels will be critical to intensify action for promoting the health of migrants on the road to achieving the end TB targets.

Latent tuberculosis infection: An overview.

Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis (TB) disease. Individuals with LTBI represent a reservoir for active TB cases. The detection and management of LTBI is now a key component of the World Health Organization's End TB Strategy and the Government of Canada's federal framework for action on TB prevention and control. This is because people with LTBI can progress to active TB or undergo reactivation, a risk that is greatly increased in those with immunocompromising conditions. This overview provides a summary of LTBI and reactivation risk, as well as the recent advances in the diagnosis and treatment of LTBI.

Beyond pills and tests: addressing the social determinants of tuberculosis

Poverty drives tuberculosis (TB) rates but the approach to TB control has been disproportionately biomedical. In 2015, the World Health Organization's End TB Strategy explicitly identified the need to address the social determinants of TB through socio-economic interventions. However, evidence concerning poverty reduction and cost mitigation strategies is limited. The research described in this article, based on the 2016 Royal College of Physicians Linacre Lecture, aimed to address this knowledge gap. The research was divided into two phases: the first phase was an analysis of a cohort study identifying TB-related costs of TB-affected households and creating a clinically relevant threshold above which those costs became catastrophic; the second was the design, implementation and evaluation of a household randomised controlled evaluation of socio-economic support to improve access to preventive therapy, increase TB cure, and mitigate the effects of catastrophic costs. The first phase showed TB remains a disease of people living in poverty - 'free' TB care was unaffordable for impoverished TB-affected households and incurring catastrophic costs was associated with as many adverse TB treatment outcomes (including death, failure of treatment, lost to follow-up and TB recurrence) as multidrug resistant (MDR) TB. The second phase showed that, in TB-affected households receiving socio-economic support, household contacts were more likely to start and adhere to TB preventive therapy, TB patients were more likely to be cured and households were less likely to incur catastrophic costs. In impoverished Peruvian shantytowns, poverty remains inextricably linked with TB and incurring catastrophic costs predicted adverse TB treatment outcome. A novel socio-economic support intervention increased TB preventive therapy uptake, improved TB treatment success and reduced catastrophic costs. The impact of the intervention on TB control is currently being evaluated by the Community Randomized Evaluation of a Socio-economic Intervention to Prevent TB (CRESIPT) study.

Sputum smear microscopy result: a predictor for drug-resistant tuberculosis?

Until countries establish capacity for continuous surveillance systems, representative surveys of tuberculosis (TB) patients continue to improve our understanding of the burden of drug-resistant TB and help ensure appropriate allocation of resources. Although the available data are limited, the current recommendation of restricting surveys to sputum smear-positive patients is justified, given the greatly simplified logistics and only limited evidence in specific settings of an association between drug resistance and sputum smear status. Nonetheless, the relationship between drug resistance and sputum smear microscopy results may vary according to the setting and population under study. With the increasing availability and use of molecular diagnostics and the drive for universal drug susceptibility testing under the World Health Organization's End TB Strategy, substantially more data on drug resistance in the whole TB patient population should become available in the near future.